Rosucard 10 mg, 90 film-coated tablets

Nosological classification (ICD-10)

• E78.0 Pure hypercholesterolemia
• E78.1 Pure hyperglyceridemia
• E78.2 Mixed hyperlipidemia
• E78.5 Hyperlipidemia, unspecified
• I10 Essential (primary) hypertension
• I15 Secondary hypertension
• I21 Acute myocardial infarction
• I25 Chronic ischemic heart disease
• I64 Stroke not specified as hemorrhage or infarction
• I70 Atherosclerosis
• Z72.0 Tobacco use
• Z82.4 Family history of coronary heart disease and other diseases of the cardiovascular system

Compound

Pharmacodynamics

A lipid-lowering drug from the group of statins. A selective competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, an enzyme that converts HMG-CoA into mevalonate, a precursor of cholesterol (CH).

Increases the number of LDL receptors on the surface of hepatocytes, which leads to increased uptake and catabolism of LDL, inhibition of VLDL synthesis, reducing the total concentration of LDL and VLDL. Reduces the concentrations of LDL-C, high-density non-lipoprotein cholesterol (non-HDL-C), VLDL-C, total cholesterol, triglycerides (TG), VLDL-TG, apolipoprotein B (ApoB), reduces the LDL-C/HDL-C ratio, total Cholesterol/HDL-C, non-HDL-C/HDL-C, ApoB/apolipoprotein A-1 (ApoA-I), increases concentrations of HDL-C and ApoA-I.

The lipid-lowering effect is directly proportional to the prescribed dose.

The therapeutic effect appears within 1 week after the start of therapy, after 2 weeks it reaches 90% of the maximum, by the 4th week it reaches a maximum and after that remains constant.

Effective in adult patients with hypercholesterolemia with or without hypertriglyceridemia (regardless of race, gender or age), incl. in patients with diabetes mellitus and familial hypercholesterolemia. In 80% of patients with type IIa and IIb hypercholesterolemia (Fredrickson classification) with an average initial LDL-C concentration of about 4.8 mmol/l, when taking the drug at a dose of 10 mg, the LDL-C concentration reaches values ​​of less than 3 mmol/L.

In patients with heterozygous familial hypercholesterolemia receiving rosuvastatin at a dose of 20–80 mg/day, positive dynamics of lipid profile indicators are noted. After titration to a daily dose of 40 mg (12 weeks of therapy), a decrease in LDL-C concentrations by 53% was observed. In 33% of patients, an LDL-C concentration of less than 3 mmol/l was achieved.

In patients with homozygous familial hypercholesterolemia taking the drug at a dose of 20 and 40 mg, the average reduction in LDL-C concentrations is 22%.

In patients with hypertriglyceridemia with an initial TG concentration of 273 to 817 mg/dL, who received rosuvastatin at a dose of 5 to 40 mg once a day for 6 weeks, the concentration of TG in the blood plasma significantly decreased.

An additive effect is observed in combination with fenofibrate (in terms of reducing the concentration of TG and with nicotinic acid in lipid-lowering doses (at least 1 g/day) (in terms of reducing the concentration of HDL-C).

In the METEOR study, rosuvastatin treatment significantly slowed the rate of progression of maximum intima-media thickness (IMT) for 12 carotid artery segments compared with placebo. Compared with baseline values, a decrease in the maximum IMT value of 0.0014 mm/year was noted in the rosuvastatin group compared with an increase of 0.0131 mm/year in the placebo group. To date, a direct relationship between a decrease in IMT and a decrease in the risk of cardiovascular events has not been demonstrated.

The results of the JUPITER study showed that rosuvastatin significantly reduced the risk of developing cardiovascular complications with a relative risk reduction of 44%. The effectiveness of therapy was noted after the first 6 months of using the drug. There was a statistically significant reduction of 48% in the combined criterion, which included death from cardiovascular causes, stroke and myocardial infarction, a 54% reduction in the occurrence of fatal or non-fatal myocardial infarction and a 48% reduction in fatal or non-fatal stroke. Overall mortality decreased by 20% in the rosuvastatin group. The safety profile in patients receiving rosuvastatin 20 mg was generally similar to that in the placebo group.

Pharmacokinetics

Suction. Cmax of rosuvastatin in blood plasma is achieved approximately 5 hours after taking the drug. Absolute bioavailability is approximately 20%.

Distribution. Penetrates through the placental barrier. Rosuvastatin is absorbed primarily by the liver, which is the main site of cholesterol synthesis and LDL-C metabolism. Vd - 134 l. Plasma protein binding (mainly albumin) is approximately 90%.

Metabolism. It is biotransformed in the liver to a small extent (about 10%), being a non-core substrate for isoenzymes of the cytochrome P450 system.

The main isoenzyme involved in the metabolism of rosuvastatin is CYP2C9.

Isoenzymes CYP2C19, CYP3A4 and CYP2D6 are involved in metabolism to a lesser extent.

The main metabolites of rosuvastatin are N-dismethyl rosuvastatin and lactone metabolites.

N-dismethylrosuvastatin is approximately 50% less active than rosuvastatin; the lactone metabolites are pharmacologically inactive. More than 90% of the pharmacological activity of inhibiting circulating HMG-CoA reductase is provided by rosuvastatin, the rest is provided by its metabolites.

Excretion. About 90% of the dose of rosuvastatin is excreted unchanged through the intestines, the remainder by the kidneys. T1/2 - approximately 19 hours, does not change with increasing dose of the drug. The average plasma clearance is approximately 50 l/h (coefficient of variation - 21.7%).

As in the case of other HMG-CoA reductase inhibitors, a specific membrane transporter is involved in the process of hepatic uptake of the drug - a polypeptide that transports the organic anion OATP1B1, which plays an important role in its hepatic elimination.

Linearity. Systemic exposure of rosuvastatin increases in proportion to the dose. Pharmacokinetic parameters do not change with daily use.

Special patient groups

Kidney failure. In patients with mild to moderate renal failure, plasma concentrations of rosuvastatin or N-dismethylrosuvastatin do not change significantly. In patients with severe renal failure (Cl creatinine <30 ml/min), the concentration of rosuvastatin in the blood plasma is 3 times higher, and N-dismethylrosuvastatin is 9 times higher than in healthy volunteers. The plasma concentration of rosuvastatin in patients on hemodialysis is approximately 50% higher than in healthy volunteers.

Liver failure. In patients with a score of 7 and below on the Child-Pugh scale, an increase in T1/2 of rosuvastatin was not detected; in patients with scores of 8 and 9 on the Child-Pugh scale, a 2-fold prolongation of T1/2 was noted. There is no experience with the use of the drug in patients with more severe liver dysfunction.

Gender and age do not have a clinically significant effect on the pharmacokinetics of rosuvastatin.

Ethnic groups. The pharmacokinetic parameters of rosuvastatin depend on race: AUC in representatives of the Mongoloid race (Japanese, Chinese, Filipinos, Vietnamese and Koreans) is 2 times higher than in representatives of the Caucasian race. In Indians, the average AUC and Cmax increased by 1.3 times.

Genetic polymorphism. HMG-CoA reductase inhibitors, incl. rosuvastatin binds to the transport proteins OATP1B1 (organic anion transport polypeptide involved in the uptake of statins by hepatocytes) and BCRP (efflux transporter). Carriers of genotypes SLCO1B1 (OATP1B1) c.521CC and ABCG2 (BCRP) c.421AA showed an increase in exposure (AUC) to rosuvastatin by 1.6 and 2.4 times, respectively, compared with carriers of genotypes SLCO1B1 c.521TT and ABCG2 c .421CC.

Indications of the drug Rosucard®

primary hypercholesterolemia (Fredrickson type IIa), including heterozygous hereditary hypercholesterolemia or mixed (combined) hypercholesterolemia (Fredrickson type IIb), as an addition to diet and other non-drug treatment methods (physical exercise and weight loss) when diet therapy and non-drug methods are ineffective treatment;

homozygous hereditary hypercholesterolemia as an adjunct to dietary therapy and other lipid-lowering treatments (eg LDL apheresis), or if such treatments are not sufficiently effective;

hypertriglyceridemia (Fredrickson type IV) as an adjunct to diet;

to slow the progression of atherosclerosis as an addition to diet in patients who are indicated for therapy to reduce the concentration of total cholesterol and LDL cholesterol;

primary prevention of major cardiovascular complications (stroke, heart attack, arterial revascularization in adult patients without clinical signs of coronary heart disease, but with an increased risk of its development (age over 50 years for men and over 60 years for women, increased concentration of C-reactive protein (≥2 mg/l) in the presence of at least one of the additional risk factors, such as arterial hypertension, low HDL-C concentration, smoking, family history of early onset coronary heart disease).

Contraindications

For tablets 10 and 20 mg

hypersensitivity to rosuvastatin or other components of the drug;

liver disease in the active phase or a sustained increase in serum activity of hepatic transaminases (more than 3 times compared to ULN) of unknown origin, liver failure (severity from 7 to 9 points on the Child-Pugh scale);

an increase in the concentration of CPK in the blood by more than 5 times compared to the ULN;

hereditary diseases such as lactose intolerance, lactase deficiency or glucose-galactose malabsorption (due to the presence of lactose);

severe renal dysfunction (creatinine Cl <30 ml/min);

myopathy;

patients predisposed to the development of myotoxic complications;

simultaneous use of cyclosporine;

combined use with HIV protease inhibitors;

women of reproductive age who do not use adequate methods of contraception;

pregnancy;

lactation period;

age under 18 years (efficacy and safety have not been established).

Contraindications for 40 mg tablets (in addition to contraindications for 10 and 20 mg tablets)

The presence of the following risk factors for the development of myopathy/rhabdomyolysis:

myotoxicity due to a history of taking other HMG-CoA reductase inhibitors or fibrates;

hypothyroidism;

moderate renal failure (creatinine Cl 30–60 ml/min);

excessive alcohol consumption;

conditions that can lead to increased plasma concentrations of rosuvastatin;

simultaneous use of fibrates;

patients of the Mongoloid race;

family history of muscle diseases.

With caution (for tablets 10 and 20 mg): history of liver disease; sepsis; arterial hypotension; extensive surgical interventions; injuries; severe metabolic, endocrine or electrolyte disturbances; uncontrollable seizures; mild to moderate renal failure; hypothyroidism; history of muscle toxicity; simultaneous use of other HMG-CoA reductase inhibitors or fibrates; history of hereditary muscle diseases; age over 65 years; conditions in which an increase in the concentration of rosuvastatin in the blood plasma is noted; Mongoloid race; simultaneous administration with fibrates; excessive alcohol consumption. For 40 mg tablets: moderate renal failure (Cl creatinine >60 ml/min); age over 65 years; history of liver disease; sepsis; arterial hypotension; extensive surgical interventions; injuries; severe metabolic, endocrine or electrolyte disturbances; uncontrollable seizures.

Rosucard, 30 pcs., 10 mg, film-coated tablets

Inside,

without chewing or crushing, swallow whole with water at any time of the day, regardless of food intake.

Before starting therapy with Rosucard®, the patient should begin to follow a standard lipid-lowering diet and continue to follow it during treatment. The dose of the drug should be adjusted individually, depending on the indication and therapeutic response, taking into account current generally accepted recommendations for target lipid levels. If it is necessary to take the drug at a dose of 5 mg, the 10 mg tablet should be divided into 2 parts according to the risk.

The recommended starting dose of Rosucard® for patients starting to take the drug, or for patients transferred from taking other HMG-CoA reductase inhibitors, is 5 or 10 mg 1 time per day.

When choosing the initial dose, one should be guided by the patient’s cholesterol level and take into account the risk of developing cardiovascular complications, and it is also necessary to assess the potential risk of side effects. If necessary, after 4 weeks the dose of the drug can be increased.

Due to the potential for side effects when taking a dose of 40 mg compared to lower doses of the drug (see "Side Effects"), final titration to a maximum dose of 40 mg should only be done in patients with severe hypercholesterolemia and a high risk of cardiovascular complications (especially in patients with hereditary hypercholesterolemia) in whom the target cholesterol level was not achieved when taking a dose of 20 mg and who will be under medical supervision. Particularly careful monitoring of patients receiving the drug at a dose of 40 mg is recommended.

It is not recommended to prescribe a dose of 40 mg to patients who have not previously consulted a doctor. After 2–4 weeks of therapy and/or when the dose of Rosucard® is increased, it is necessary to monitor lipid metabolism parameters (if necessary, dose adjustment is required).

Patients with liver failure.

In patients with liver failure with Child-Pugh scores below 7 points, no dose adjustment of Rosucard® is required. The drug Rosucard® is contraindicated in patients with liver disease in the active phase, a persistent increase in serum activity of liver transaminases (more than 3 times compared to ULN) of unknown origin and patients with liver failure (severity from 7 to 9 points on the Child-Pugh scale ) (see “Contraindications”).

Patients with renal failure.

In patients with mild renal failure, no dose adjustment is required. The recommended initial dose of Rosucard® is 5 mg/day.

In patients with severe renal failure (creatinine clearance <30 ml/min), the use of Rosucard® is contraindicated.

In patients with moderate renal failure (creatinine clearance 30–60 ml/min), the use of Rosucard® at a dose of 40 mg/day is contraindicated (see “Contraindications”).

Elderly patients.

In patients over 65 years of age, no dose adjustment is required.

Special populations

Patients with a predisposition to myopathy.

The use of Rosucard® at a dose of 40 mg/day is contraindicated in patients with a predisposition to myopathy (see “Contraindications”). When prescribing doses of 10 and 20 mg/day, the recommended initial dose of Rosucard® for this group of patients is 5 mg/day.

Ethnic groups.

When studying the pharmacokinetic parameters of rosuvastatin, an increase in the systemic concentration of the drug was noted in representatives of the Mongoloid race (see “Pharmacokinetics”).

This fact should be taken into account when prescribing Rosucard® to patients of the Mongoloid race. When prescribing doses of 10 and 20 mg, the recommended initial dose of Rosucard® for this group of patients is 5 mg/day. The use of the drug Rosucard® at a dose of 40 mg/day in representatives of the Mongoloid race is contraindicated (see “Contraindications”).

When prescribing Rosucard® with gemfibrozil, the dose should not exceed 10 mg/day.

Genetic polymorphism.

Carriers of the SLCO1B1 (OATP1B1) c.521CC and ABCG2 (BCRP) c.421AA genotypes showed an increase in exposure (AUC) to rosuvastatin compared to carriers of the SLC01B1 c.521TT and ABCG2 c.421CC genotypes. For patients carrying genotypes c.521CC or c.421AA, the recommended maximum dose of Rosucard® is 20 mg/day (see “Pharmacokinetics”, “Special instructions” and “Interaction”).

Concomitant therapy.

Rosucard® binds to various transport proteins (in particular, OATP1B1 and BCRP). When simultaneous use of the drug Rosucard® with drugs (such as cyclosporine, some HIV protease inhibitors, including a combination of ritonavir with atazanavir, lopinavir and/or tipranavir) that increase the concentration of rosuvastatin in the blood plasma due to interaction with transport proteins, the risk of developing myopathy may increase (including rhabdomyolysis) (see “Special Instructions” and “Interaction”). In such cases, the possibility of prescribing alternative therapy or temporarily stopping the use of Rosucard® should be assessed. If the use of the above drugs is necessary, you should read the instructions for use of the drugs before prescribing them simultaneously with the drug Rosucard®, assess the benefit-risk ratio of concomitant therapy and consider reducing the dose of the drug Rosucard® (see “Interaction”).

Use during pregnancy and breastfeeding

The use of Rosucard® in women of reproductive age is possible only if reliable methods of contraception are used and if the patient is informed about the possible risk of treatment to the fetus.

Since cholesterol and substances synthesized from cholesterol are important for fetal development, the potential risk of inhibiting HMG-CoA reductase outweighs the benefit of using the drug during pregnancy.

Rosucard® is contraindicated during pregnancy and lactation. If pregnancy is diagnosed during therapy, the use of the drug Rosucard® should be stopped immediately, and the patient should be warned about the potential risk to the fetus.

If it is necessary to use the drug during lactation, taking into account the possibility of adverse events in infants, the issue of stopping breastfeeding should be decided.

Rosecard

Use during pregnancy and breastfeeding

Rosucard® is contraindicated during pregnancy and lactation (breastfeeding).
The use of Rosucard® in women of reproductive age is possible only if reliable methods of contraception are used and if the patient is informed about the possible risk of treatment to the fetus.

Since cholesterol and substances synthesized from cholesterol are important for fetal development, the potential risk of inhibiting HMG-CoA reductase outweighs the benefit of using the drug during pregnancy. If pregnancy is diagnosed during drug therapy, the use of Rosucard® should be stopped immediately, and the patient should be warned about the potential risk to the fetus.

If it is necessary to use the drug during lactation, taking into account the possibility of adverse events in infants, the issue of stopping breastfeeding should be decided.

Use for liver dysfunction

Contraindications for tablets 10 and 20 mg: liver disease in the active phase or a persistent increase in the activity of liver transaminases in the serum (more than 3 times compared to ULN) of unknown origin; liver failure (severity from 7 to 9 points on the Child-Pugh scale).

Use for renal impairment

Contraindications for tablets 10 and 20 mg: severe renal dysfunction (creatinine clearance less than 30 ml/min); for 40 mg tablets: moderate renal failure (creatinine clearance 30-60 ml/min).

special instructions

During treatment, especially during the period of dose adjustment of the drug Rosucard®, the lipid profile should be monitored every 2-4 weeks and the dose of the drug should be changed if necessary.

It is recommended to determine liver function indicators before starting therapy and 3 months after starting therapy. The use of Rosucard® should be discontinued or the dose reduced if the level of hepatic transaminase activity in the blood serum is 3 times higher than the ULN.

When using the drug Rosucard® at a dose of 40 mg, it is recommended to monitor kidney function indicators.

In patients with hypercholesterolemia due to hypothyroidism or nephrotic syndrome, treatment of underlying diseases should be carried out before starting treatment with Rosucard®.

In patients with existing risk factors for the development of rhabdomyolysis, it is necessary to consider the balance of expected benefit and potential risk and conduct clinical monitoring throughout the course of treatment.

The patient should be informed to immediately report to the doctor the unexpected onset of muscle pain, muscle weakness or cramps, especially in combination with malaise and fever. In such patients, CPK activity should be determined. Therapy should be discontinued if CPK activity is significantly increased (more than 5 times the ULN) or if muscle symptoms are severe and cause daily discomfort. If symptoms disappear and CPK activity returns to normal, then re-prescribing Rosucard® or other HMG-CoA reductase inhibitors in lower doses should be considered with careful monitoring of the patient.

Determination of CPK activity should not be carried out after intense physical activity or in the presence of other possible reasons for increased CPK activity, which may lead to incorrect interpretation of the results obtained. If the initial CPK activity is significantly increased, then a repeat measurement should be taken after 5-7 days; therapy should not be started if a repeat test confirms the initial CPK activity (5 times higher than normal).

Routine monitoring of CPK activity in the absence of symptoms is impractical.

An increased incidence of myositis and myopathy has been reported in patients taking other HMG-CoA reductase inhibitors in combination with fibrates (including gemfibrozil), cyclosporine, niacin, azole antifungals, protease inhibitors and macrolide antibiotics. The ratio of expected benefits and potential risks should be carefully weighed when using the drug Rosucard® and fibrates or nicotinic acid (at least 1 g / day); Co-administration of gemfibrozil is not recommended.

In most cases, proteinuria decreases or disappears during therapy and does not indicate the occurrence of acute or exacerbation of existing kidney disease. Renal function should be assessed during routine examination of patients receiving the drug at a dose of 40 mg.

Drugs of the statin class can cause an increase in blood glucose concentrations. In some patients at high risk of developing diabetes mellitus, such changes may lead to its manifestation, which is an indication for hypoglycemic therapy. However, the reduction in the risk of vascular diseases during the use of statins exceeds the risk of developing diabetes mellitus, so this factor should not serve as a basis for discontinuing statin treatment. Patients at risk (fasting glucose concentration 5.6-6.9 mmol/l, body mass index (BMI) >30 kg/m2, hypertriglyceridemia, history of arterial hypertension) should be under medical supervision and regularly monitor biochemical parameters.

The simultaneous administration of rosuvastatin and HIV protease inhibitors is not recommended.

Isolated cases of interstitial lung disease have been reported with long-term use of rosuvastatin. If interstitial lung disease is suspected, therapy with Rosucard® should be discontinued.

When studying the pharmacokinetic parameters of rosuvastatin, an increase in the systemic concentration of the drug was noted in representatives of the Mongoloid race. This fact should be taken into account when prescribing Rosucard® to patients of the Mongoloid race.

Impact on the ability to drive vehicles and operate machinery

Patients should be careful when driving vehicles and doing activities that require increased concentration and speed of psychomotor reactions (dizziness may occur during therapy).

Side effects

The following is an adverse reaction profile for rosuvastatin based on clinical trial data and extensive post-marketing experience.

The frequency of adverse reactions was determined according to the following gradation (WHO classification): very often - >1/10; often - from >1/100 to <1/10; uncommon - from >1/1000 to <1/100; rarely - from >1/10000 to <1/1000; very rarely - from <1/10000, including individual reports; frequency unknown (it is not possible to determine the frequency from the available data).

From the blood and lymphatic system: rarely - thrombocytopenia.

From the nervous system: often - headache, dizziness; very rarely - peripheral neuropathy, memory loss or decline; frequency unknown - sleep disturbances, including insomnia and nightmares.

Mental disorders: frequency unknown - depression.

From the digestive system: often - nausea, constipation, abdominal pain; infrequently - vomiting; rarely - pancreatitis; frequency unknown - diarrhea.

From the liver and biliary tract: rarely - transient increase in the activity of AST and ALT; very rarely - hepatitis, jaundice.

From the respiratory system: frequency unknown - cough, dyspnea.

From the immune system: rarely - hypersensitivity reactions, including angioedema.

From the musculoskeletal and connective tissue side: often - myalgia; rarely - myopathy (including myositis), rhabdomyolysis (in patients treated in doses >20 mg/day); very rarely - arthralgia; frequency unknown - immune-mediated necrotizing myopathy.

For the skin and subcutaneous tissues: infrequently - itching, urticaria, skin rash; frequency unknown - Stevens-Johnson syndrome.

From the kidneys and urinary tract: often - proteinuria (observed in less than 1% of patients receiving a dose of the drug 10-20 mg / day, and in approximately 3% of patients receiving 40 mg / day), decreasing during therapy and not associated with the occurrence of kidney disease, urinary tract infections; very rarely - hematuria.

From the genital organs and breast: very rarely - gynecomastia.

Impact on indicators of laboratory and instrumental studies: infrequently - a transient dose-dependent increase in serum CPK activity, with an increase of more than 5 times compared to the ULN, therapy should be temporarily suspended, an increase in the concentration of glycosylated hemoglobin in the blood plasma.

Other: often - asthenia; frequency unknown - peripheral edema.

As with the use of other HMG-CoA reductase inhibitors, the incidence is dose-dependent, side effects are usually mild and go away on their own.

When using the drug Rosucard®, changes in the following laboratory parameters were observed: increased concentrations of glucose, bilirubin, alkaline phosphatase activity, GGT.

The following adverse events have been reported with some statins: erectile dysfunction; isolated cases of interstitial lung disease (especially with long-term use); diabetes mellitus type 2 (frequency depends on the presence or absence of risk factors - fasting blood glucose concentration 5.6–6.9 mmol/l, body mass index (BMI) >30 kg/m2, hypertriglyceridemia, history of arterial hypertension).

Rosucard 10 mg, 90 film-coated tablets

Registration Certificate Holder

SANOFI RUSSIA (Russia)

Dosage form

Medicine - Rosucard®

Description

Film-coated tablets

light pink, oblong, biconvex, with a notch.

1 tab.

rosuvastatin calcium 10.4 mg, which corresponds to the content of rosuvastatin 10 mg

Excipients

: lactose monohydrate - 60 mg, microcrystalline cellulose - 45.4 mg, croscarmellose sodium - 1.2 mg, colloidal silicon dioxide - 0.6 mg, magnesium stearate - 2.4 mg.

Film shell composition:

hypromellose 2910/5 - 2.5 mg, macrogol 6000 - 0.4 mg, titanium dioxide - 0.325 mg, talc - 0.475 mg, red iron oxide dye - 0.013 mg.

10 pieces. - blisters (3) - cardboard packs. 10 pieces. - blisters (6) - cardboard packs. 10 pieces. - blisters (9) - cardboard packs.

Indications

• primary hypercholesterolemia (type IIa according to the Fredrickson classification), including familial heterozygous hypercholesterolemia, or mixed hypercholesterolemia (type IIb) - as an addition to diet when diet and other non-drug treatments (for example, exercise, weight loss) are insufficient;
• familial homozygous hypercholesterolemia - as an adjunct to diet and other lipid-lowering therapy (for example, LDL apheresis), or in cases where such therapy is not effective enough;
• hypertriglyceridemia (type IV according to the Fredrickson classification) - as an addition to the diet;
• to slow the progression of atherosclerosis - as an addition to the diet in patients who are indicated for therapy to reduce the concentration of total cholesterol and LDL cholesterol;
• primary prevention of major cardiovascular complications (stroke, heart attack, arterial revascularization) in adult patients without clinical signs of coronary artery disease, but with an increased risk of its development (age over 50 years for men and over 60 years for women, increased concentration of C-reactive protein ( ≥2 mg/l) in the presence of at least one of the additional risk factors, such as arterial hypertension, low HDL-C concentration, smoking, family history of early onset ischemic heart disease).

Contraindications for use

For tablets 10 and 20 mg

• hypersensitivity to rosuvastatin or any of the components of the drug;
• liver disease in the active phase, including a persistent increase in serum transaminase activity or any increase in serum transaminase activity (more than 3 times compared to ULN);
• severe renal dysfunction (creatinine clearance less than 30 ml/min);
• myopathy;
• simultaneous use of cyclosporine;
• in women - pregnancy, breastfeeding, lack of adequate methods of contraception;
• patients predisposed to the development of myotoxic complications;
• lactose intolerance, lactase deficiency or glucose-galactose malabsorption (the drug contains lactose);
• age under 18 years (efficacy and safety have not been established).

For tablets 40 mg

• hypersensitivity to rosuvastatin or any of the components of the drug;
• simultaneous use of cyclosporine;
• in women - pregnancy, breastfeeding, lack of adequate methods of contraception;
• liver disease in the active phase, including a persistent increase in serum transaminase activity and any increase in serum transaminase activity (more than 3 times compared with ULN), patients with risk factors for the development of myopathy/rhabdomyolysis, namely: moderate renal failure (MC) less than 60 ml/min);
• hypothyroidism;
• personal or family history of muscle diseases;
• myotoxicity due to a history of use of other HMG-CoA reductase inhibitors or fibrates.

With caution
For tablets 10 and 20 mg:
with a history of liver disease; sepsis; arterial hypotension; extensive surgical interventions; injuries; severe metabolic, endocrine or water-electrolyte disorders; uncontrollable seizures; for mild to moderate renal failure; hypothyroidism; data on a history of muscle toxicity when using other HMG-CoA reductase inhibitors or fibrates; history of hereditary muscle diseases; conditions in which an increase in the concentration of rosuvastatin in the blood plasma is noted; when used simultaneously with fibrates; when used simultaneously with HIV protease inhibitors; in patients over 65 years of age; in patients of the Mongoloid race; with excessive alcohol consumption.

For 40 mg tablets:

with mild renal failure (creatinine clearance more than 60 ml/min); history of liver diseases; sepsis; arterial hypotension; extensive surgical interventions; injuries; severe metabolic, endocrine or water-electrolyte disorders; uncontrollable seizures; in patients over 65 years of age.

pharmachologic effect

A lipid-lowering drug from the statin group. A selective competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, an enzyme that converts HMG-CoA into mevalonate, a precursor of cholesterol (Cc).

Increases the number of LDL receptors on the surface of hepatocytes, which leads to increased uptake and catabolism of LDL, inhibition of VLDL synthesis, reducing the total concentration of LDL and VLDL. Reduces the concentrations of LDL-C, high-density non-lipoprotein cholesterol (non-HDL-C), VLDL-C, total cholesterol, TG, VLDL-TG, apolipoprotein B (ApoB), reduces the ratio of LDL-C/HDL-C, total cholesterol/C. -HDL, non-HDL-C/HDL-C, ApoB/apolipoprotein A-1 (ApoA-1), increases the concentrations of HDL-C and ApoA-1.

The lipid-lowering effect is directly proportional to the prescribed dose. The therapeutic effect appears within 1 week after the start of therapy, after 2 weeks it reaches 90% of the maximum, by 4 weeks it reaches a maximum and after that remains constant.

Clinical effectiveness

Effective in adult patients with hypercholesterolemia with or without hypertriglyceridemia (regardless of race, gender or age), incl. in patients with diabetes mellitus and familial hypercholesterolemia. In 80% of patients with hypercholesterolemia type IIa and IIb (according to the Fredrickson classification) with an average initial LDL-C concentration of about 4.8 mmol/l, while taking the drug at a dose of 10 mg, the LDL-C concentration reaches values ​​of less than 3 mmol/l.

In patients with heterozygous familial hypercholesterolemia receiving rosuvastatin at a dose of 20-80 mg/day, positive dynamics of lipid profile indicators are noted.

An additive effect is observed in combination with fenofibrate in relation to the concentration of TG and with nicotinic acid in lipid-lowering doses (more than 1 g/day) in relation to the reduction in the concentration of HDL-C.

Drug interactions

The effect of the use of other drugs on rosuvastatin

Transport protein inhibitors:

rosuvastatin binds to certain transport proteins, in particular OATP1B1 and BCRP. Concomitant use of drugs that are inhibitors of transport proteins may be accompanied by an increase in the concentration of rosuvastatin in the blood plasma and an increased risk of developing myopathy (see table).

Cyclosporine:

with simultaneous use of rosuvastatin and cyclosporine, the AUC of rosuvastatin was on average 7 times higher than the value observed in healthy volunteers (see table). Does not affect plasma concentrations of cyclosporine. Rosucard® is contraindicated in patients taking cyclosporine.

HIV protease inhibitors:

Although the exact mechanism of interaction is unknown, concomitant use of HIV protease inhibitors may lead to a significant increase in rosuvastatin exposure (see table). A pharmacokinetic study of co-administration of rosuvastatin 20 mg and a combination drug containing two HIV protease inhibitors (400 mg lopinavir/100 mg ritonavir) in healthy volunteers resulted in approximately two-fold and five-fold increases in rosuvastatin AUC(0-24) and Cmax, respectively. Therefore, simultaneous use of Rosucard® and HIV protease inhibitors is not recommended (see table).

Gemfibrozil and other lipid-lowering drugs:

The combined use of rosuvastatin and gemfibrozil leads to a 2-fold increase in Cmax and AUC of rosuvastatin. Based on specific interaction data, a pharmacokinetically significant interaction with fenofibrate is not expected, but a pharmacodynamic interaction is possible. Gemfibrozil, fenofibrate, other fibrates and nicotinic acid in lipid-lowering doses (more than 1 g/day) increase the risk of myopathy when used simultaneously with HMG-CoA reductase inhibitors, possibly due to the fact that they can cause myopathy and when used in as monotherapy. When taking the drug simultaneously with gemfibrozil, fibrates, nicotinic acid in lipid-lowering doses, patients are recommended to take an initial dose of Rosucard® 5 mg; taking a dose of 40 mg is contraindicated when co-administered with fibrates.

Fusidic acid:

There have been no specific drug interaction studies between fusidic acid and rosuvastatin, but isolated case reports of rhabdomyolysis have been noted.

Ezetimibe:

simultaneous use of Rosucard® at a dose of 10 mg and ezetimibe at a dose of 10 mg was accompanied by an increase in the AUC of rosuvastatin in patients with hypercholesterolemia (see table). An increased risk of side effects due to the pharmacodynamic interaction between Rosucard® and ezetimibe cannot be excluded.

Antacids:

simultaneous use of rosuvastatin and antacid suspensions containing aluminum or magnesium hydroxide leads to a decrease in the plasma concentration of rosuvastatin by approximately 50%. This effect is less pronounced if antacids are used 2 hours after taking rosuvastatin. The clinical significance of this interaction has not been studied.

Erythromycin:

simultaneous use of rosuvastatin and erythromycin leads to a decrease in AUC of rosuvastatin by 20% and Cmax of rosuvastatin by 30%. This interaction may occur as a result of increased intestinal motility caused by erythromycin.

Isoenzymes of the cytochrome P450 system:

the results of in vivo and in vitro studies showed that rosuvastatin is neither an inhibitor nor an inducer of cytochrome P450 isoenzymes. In addition, rosuvastatin is a weak substrate for these enzymes. Therefore, interaction of rosuvastatin with other drugs at the metabolic level involving cytochrome P450 isoenzymes is not expected. There was no clinically significant interaction between rosuvastatin and fluconazole (inhibitor of CYP2C9 and CYP3A4 isoenzymes) and ketoconazole (inhibitor of CYP2A6 and CYP3A4 isoenzymes).

Interactions with drugs that require dose adjustment of rosuvastatin (see table)

The dose of Rosucard® should be adjusted if it is necessary to use it together with drugs that increase the exposure of rosuvastatin. If an increase in exposure by 2 times or more is expected, the initial dose of Rosucard® should be 5 mg 1 time / day. The maximum daily dose of Rosucard® should also be adjusted so that the expected exposure to rosuvastatin does not exceed that for a dose of 40 mg taken without the simultaneous administration of drugs that interact with rosuvastatin. For example, the maximum daily dose of Rosucard® when used simultaneously with gemfibrozil is 20 mg (increased exposure by 1.9 times), with ritonavir/atazanavir - 10 mg (increased exposure by 3.1 times).

Table. Effect of concomitant therapy on rosuvastatin exposure (AUC, data in descending order) - results of published clinical studies

Concomitant therapy regimen Rosuvastatin regimen Change in rosuvastatin AUC

Cyclosporine 75-200 mg 2 times/day, 6 months 10 mg 1 time/day, 10 days Increase by 7.1 times Atazanavir 300 mg/ritonavir 100 mg 1 time/day, 8 days 10 mg once Increase by 3.1 times Simeprevir 150 mg 1 time/day, 7 days 10 mg once Increased by 2.8 times Lopinavir 400 mg/ritonavir 100 mg 2 times/day, 17 days 20 mg 1 time/day, 7 days Increased by 2.1 times Clopidogrel 300 mg, then 75 mg for 24 hours 20 mg once Increased by 2 times Gemfibrozil 600 mg 2 times/day , 7 days 80 mg once Increase by 1.9 times Eltrombopag 75 mg 1 time / day, 10 days 10 mg once Increase by 1.6 times Darunavir 600 mg / ritonavir 100 mg 2 times / day, 7 days 10 mg 1 time / day, 7 days Increase by 1.5 times Tipranavir 500 mg / ritonavir 200 mg 2 times/day, 11 days 10 mg once 1.4-fold increase Dronedarone 400 mg 2 times/day No data 1.4-fold increase Itraconazole 200 mg 1 time/day, 5 days 10 mg or 80 mg once 1.4-fold increase Ezetimibe 10 mg 1 time/day, 14 days 10 mg 1 time/day, 14 days Increase 1.2 times Fosamprenavir 700 mg/ritonavir 100 mg 2 times/day, 8 days 10 mg once No changes Aleglitazar 0.3 mg, 7 days 40 mg, 7 days No changes Silymarin 140 mg 3 times/day, 5 days 10 mg once No changes Fenofibrate 67 mg 3 times/day, 7 days10 mg, 7 daysNo changesRifampin 450 mg 1 time/day, 7 days20 mg onceNo changesKetoconazole 200 mg 2 times/day, 7 days80 mg onceNo changesFluconazole 200 mg 1 time/day, 11 days80 mg onceNo changesErythromycin 500 mg 4 times/day, 7 days 80 mg once, 28% reduction Baikalin 50 mg 3 times/day, 14 days 20 mg once, 47% reduction

The effect of rosuvastatin on other drugs

Vitamin K antagonists:

Initiating therapy or increasing the dose of Rosucard® in patients receiving concomitant vitamin K antagonists (for example, warfarin) may lead to an increase in the INR. Discontinuation or reduction of the dose of Rosucard® may cause a decrease in INR. In such cases, INR monitoring is recommended.

Oral contraceptives/hormone replacement therapy:

simultaneous use of rosuvastatin and oral contraceptives increases the AUC of ethinyl estradiol and AUC of norgestrel by 26% and 34%, respectively.
This increase in plasma concentration should be taken into account when selecting the dose of oral contraceptives. There are no pharmacokinetic data on the simultaneous use of Rosucard® and hormone replacement therapy; therefore, a similar effect cannot be excluded when using this combination.
However, this combination was widely used during clinical trials and was well tolerated by patients. Other medicines:

No clinically significant interaction between rosuvastatin and digoxin is expected.

Dosage regimen

The drug is taken orally. The tablets should be swallowed whole, without chewing or crushing, with water, at any time of the day, regardless of meals.

Before starting therapy with Rosucard®, the patient should begin to follow a standard lipid-lowering diet and continue to follow it during treatment.

The dose of the drug should be individualized depending on the indication and therapeutic response, taking into account current generally accepted recommendations for target lipid concentrations.

The recommended starting dose of Rosucard® for patients starting to take the drug, or for patients transferred from taking other HMG-CoA reductase inhibitors, is 5 or 10 mg 1 time / day. If it is necessary to take the drug Rosucard® at a dose of 5 mg, the 10 mg tablet should be divided into two parts according to the risk.

When choosing an initial dose, one should be guided by the patient's cholesterol level and take into account the risk of developing cardiovascular complications, and the potential risk of side effects should be assessed. If necessary, after 4 weeks the dose of the drug can be increased.

Due to the possible development of side effects, final titration to a maximum dose of 40 mg should be carried out only in patients with severe hypercholesterolemia and a high risk of cardiovascular complications (especially patients with hereditary hypercholesterolemia) who did not experience symptoms when taking the drug at a dose of 20 mg. the target cholesterol concentration has been achieved. Such patients should be under medical supervision. Particularly careful monitoring of patients receiving the drug at a dose of 40 mg is recommended.

It is not recommended to prescribe a dose of 40 mg to patients who have not previously consulted a doctor. After 2-4 weeks of therapy and/or when increasing the dose of the drug Rosucard®, it is necessary to monitor lipid metabolism parameters (if necessary, dose adjustment is required).

In elderly patients over 65 years of age

no dose adjustment is required.

The drug is contraindicated in patients with active liver disease

.

In patients with mild renal failure

no dose adjustment is required;
The recommended initial dose of Rosucard® is 5 mg/day. In patients with moderate renal failure (creatinine clearance 30-60 ml/min),
the use of Rosucard® at a dose of 40 mg/day is contraindicated.
In patients with severe renal failure (creatinine clearance less than 30 ml/min),
the use of Rosucard® is contraindicated.

In patients with a predisposition to myopathy

the use of Rosucard® at a dose of 40 mg/day is contraindicated. When prescribing the drug in doses of 10 mg and 20 mg/day, the recommended initial dose for this group of patients is 5 mg/day.

When studying the pharmacokinetic parameters of rosuvastatin, an increase in the systemic concentration of the drug was noted in representatives of the Mongoloid race

.
This fact should be taken into account when prescribing Rosucard® to patients of the Mongoloid race. When prescribing the drug in doses of 10 mg and 20 mg, the recommended initial dose for this group of patients is 5 mg/day. The use of the drug Rosucard® at a dose of 40 mg/day in representatives of the Mongoloid race is contraindicated. Genetic polymorphism.
Carriers of the SLCO1B1 (OATP1B1) c.521CC and ABCG2 (BCRP) c.421AA genotypes had an increase in rosuvastatin exposure (AUC) compared to carriers of the SLC01B1 c.521TT and ABCG2 c.421CC genotypes. For patients carrying genotypes c.521CC or c.421AA, the recommended maximum dose of Rosucard® is 20 mg/day.

Concomitant therapy.

Rosuvastatin binds to various transport proteins (in particular, OATP1B1 and BCRP). When simultaneous use of the drug Rosucard® with drugs (such as cyclosporine, some HIV protease inhibitors, including a combination of ritonavir with atazanavir, lopinavir and/or tipranavir) that increase the concentration of rosuvastatin in the blood plasma due to interaction with transport proteins, the risk of developing myopathy may increase (including rhabdomyolysis). In such cases, the possibility of prescribing alternative therapy or temporarily stopping the use of Rosucard® should be assessed. If the use of the above drugs is necessary, you should read the instructions for use of the drugs before prescribing them simultaneously with the drug Rosucard®, assess the benefit-risk ratio of concomitant therapy and consider reducing the dose of the drug Rosucard®.

Overdose

When taking several daily doses simultaneously, the pharmacokinetic parameters of rosuvastatin do not change.

Treatment:

There is no specific treatment; symptomatic therapy is carried out to maintain the functions of vital organs and systems. Monitoring of liver function indicators and CPK activity is necessary. Hemodialysis is ineffective.

Side effect

Side effects observed when taking rosuvastatin are usually mild and go away on their own. As with other HMG-CoA reductase inhibitors, the incidence of side effects is mainly dose-dependent.

The following is an adverse reaction profile for rosuvastatin based on clinical trial data and extensive post-marketing experience.

Determination of the frequency of adverse reactions (according to the WHO classification): very often (≥1/10), often (from ≥1/100 to <1/10), infrequently (≥1/1000 to <1/100), rarely ( from ≥1/10,000 to <1/1000), very rare (from <1/10,000, including isolated reports), frequency unknown (it is not possible to determine the frequency from the available data).

From the hematopoietic system:

rarely - thrombocytopenia.

From the nervous system:

often - headache, dizziness; very rarely - peripheral neuropathy, memory loss or decline; frequency unknown - sleep disturbances, including insomnia and nightmares.

Mental disorders:

frequency unknown - depression.

From the digestive system:

often - nausea, constipation, abdominal pain; infrequently - vomiting; rarely - pancreatitis; frequency unknown - diarrhea.

From the liver and biliary tract:

rarely - a dose-dependent transient increase in the activity of AST and ALT; very rarely - hepatitis, jaundice.

From the respiratory system:

frequency unknown - cough, dyspnea.

From the musculoskeletal system:

often - myalgia; rarely - myopathy (including myositis), rhabdomyolysis with and without acute renal failure (in patients treated in doses >20 mg/day); very rarely - arthralgia; frequency unknown - immune-mediated necrotizing myopathy.

Allergic reactions:

infrequently - skin itching, urticaria; rarely - hypersensitivity reactions, including angioedema.

From the skin and subcutaneous tissue:

uncommon - rash; frequency unknown - Stevens-Johnson syndrome.

From the urinary system:

often - proteinuria; very rarely - hematuria. Changes in the amount of protein in the urine (from none or trace amounts to ++ or more) are observed in less than 1% of patients receiving a dose of 10-20 mg/day and in approximately 3% of patients receiving 40 mg/day. Proteinuria decreases with therapy and is not associated with kidney disease or urinary tract infection.

From the genital organs and breast:

very rarely - gynecomastia.

Laboratory indicators:

infrequently - a dose-dependent increase in serum CPK activity (in most cases, slight, asymptomatic and temporary). If the activity increases by more than 5 times compared to the ULN, therapy with Rosucard® should be temporarily suspended. Increased concentration of glycosylated hemoglobin in blood plasma.

Other:

often - asthenic syndrome;
frequency unknown - peripheral edema. When using the drug Rosucard®, changes in the following laboratory parameters were observed: increased concentrations of glucose, bilirubin, alkaline phosphatase activity, GGT.
The following adverse events have been reported with the use of some statins: erectile dysfunction, isolated cases of interstitial lung disease (especially with long-term use), type 2 diabetes mellitus, the incidence of which depends on the presence or absence of risk factors (fasting blood glucose concentration 5.6- 6.9 mmol/l, BMI >30 kg/m2, hypertriglyceridemia, history of arterial hypertension).

special instructions

Effect on the kidneys

In patients receiving high doses of rosuvastatin (mainly 40 mg), tubular proteinuria was observed, which in most cases was transient. This proteinuria did not indicate acute kidney disease or progression of kidney disease. In patients taking the drug at a dose of 40 mg, it is recommended to monitor renal function parameters during treatment.

Effect on the musculoskeletal system

The following musculoskeletal effects have been reported with rosuvastatin at all doses, and particularly at doses greater than 20 mg: myalgia, myopathy, and in rare cases, rhabdomyolysis.

Determination of CPK activity

Determination of CPK activity should not be carried out after intense physical activity or in the presence of other possible reasons for increased CPK activity, which may lead to incorrect interpretation of the results obtained. If the initial CPK activity is significantly increased (5 times higher than ULN), a repeat measurement should be taken after 5-7 days. Therapy should not be started if a repeat test confirms initial CPK activity (more than 5 times the ULN).

Before starting therapy

When using the drug Rosucard®, as well as when using other HMG-CoA reductase inhibitors, caution should be exercised in patients with existing risk factors for myopathy/rhabdomyolysis. The risk-benefit ratio should be assessed and, if therapy is necessary, clinical monitoring of the patient should be carried out during treatment.

During therapy

The patient should be informed to immediately report to the doctor the unexpected onset of muscle pain, muscle weakness or cramps, especially in combination with malaise and fever. In such patients, CPK activity should be determined. Therapy should be discontinued if CK activity is significantly elevated (more than 5 times the ULN) or if muscle symptoms are severe and cause daily discomfort (even if CK activity is increased less than 5 times the ULN). If symptoms disappear and CPK activity returns to normal, re-prescribing Rosucard® or other HMG-CoA reductase inhibitors in lower doses should be considered with careful monitoring of the patient.

Routine monitoring of CPK activity in the absence of symptoms is impractical.

Very rare cases of immune-mediated necrotizing myopathy have been reported with clinical manifestations in the form of persistent weakness of the proximal muscles and increased CPK activity in the blood serum during treatment or upon discontinuation of statins, incl. rosuvastatin. Additional studies of the muscular and nervous system, serological studies, and therapy with immunosuppressive drugs may be required. There were no signs of increased effects on skeletal muscles when taking rosuvastatin and concomitant therapy. However, an increase in the number of cases of myositis and myopathy has been reported in patients taking other HMG-CoA reductase inhibitors in combination with fibric acid derivatives, including gemfibrozil, cyclosporine, nicotinic acid in hypolipidemic doses (more than 1 g / day), azole antifungals, inhibitors HIV proteases and macrolide antibiotics. Gemfibrozil increases the risk of myopathy when used together with certain HMG-CoA reductase inhibitors. Thus, the simultaneous use of Rosucard® and gemfibrozil is not recommended. The risk/benefit ratio should be carefully weighed when using Rosucard® together with fibrates or lipid-lowering doses of nicotinic acid. Taking Rosucard® at a dose of 40 mg together with fibrates is contraindicated. 2-4 weeks after the start of treatment and/or when increasing the dose of the drug Rosucard®, monitoring of lipid metabolism parameters is necessary (if necessary, dose adjustment is required).

Liver

It is recommended to determine liver function indicators before starting therapy and 3 months after starting therapy. Taking Rosucard® should be stopped or the dose reduced if the activity of hepatic transaminases in the blood plasma is 3 times higher than the ULN.

In patients with hypercholesterolemia due to hypothyroidism or nephrotic syndrome, treatment of underlying diseases should be carried out before starting treatment with Rosucard®.

HIV protease inhibitors

Concomitant use of Rosucard® with HIV protease inhibitors is not recommended.

Interstitial lung disease

Isolated cases of interstitial lung disease have been reported with some statins, especially over long periods of use. Manifestations of the disease may include shortness of breath, nonproductive cough and deterioration in general health (weakness, weight loss and fever). If interstitial lung disease is suspected, therapy with Rosucard® should be discontinued.

Diabetes mellitus type 2

Drugs of the statin class can cause an increase in blood glucose concentrations. In some patients at high risk of developing diabetes mellitus, such changes may lead to its manifestation, which is an indication for hypoglycemic therapy. However, the reduction in the risk of vascular diseases while taking statins exceeds the risk of developing diabetes, so this factor should not serve as a basis for discontinuing statin treatment. Patients at risk (fasting blood glucose concentration 5.6-6.9 mmol/l, BMI >30 kg/m2, hypertriglyceridemia, history of arterial hypertension) should be under medical supervision and regularly monitor biochemical parameters.

Lactose

The drug Rosucard® should not be used in patients with lactase deficiency, galactose intolerance and glucose-galactose malabsorption.

Ethnic groups

During pharmacokinetic studies among Chinese and Japanese patients, an increase in systemic concentrations of rosuvastatin was observed compared with values ​​​​obtained among Caucasian patients.
Effect on the ability to drive vehicles and operate machinery
Care should be taken when driving vehicles and doing activities that require increased concentration and speed of psychomotor reactions (dizziness may occur during therapy).

Storage conditions

The drug should be stored in its original packaging out of the reach of children at a temperature not exceeding 25°C.

Best before date

Shelf life: 3 years. Do not use the drug after the expiration date.

Use during pregnancy and breastfeeding

Restrictions during pregnancy - Contraindicated. Restrictions when breastfeeding - Contraindicated.

Rosuvastatin is contraindicated during pregnancy and breastfeeding.

Use of rosuvastatin in women of reproductive age

is possible only if reliable methods of contraception are used and if the patient is informed about the possible risk of treatment to the fetus.

Since cholesterol and substances synthesized from cholesterol are important for fetal development, the potential risk of inhibiting HMG-CoA reductase outweighs the benefit of using the drug during pregnancy. If pregnancy is diagnosed during drug therapy, rosuvastatin should be stopped immediately, and the patient should be warned about the potential risk to the fetus.

If it is necessary to use the drug during lactation, given the possibility of adverse events in infants, breastfeeding should be discontinued.

Use for renal impairment

Restrictions for impaired renal function - With caution.

In patients with severe renal failure (creatinine clearance less than 30 ml/min), the use of Rosucard® is contraindicated.

In patients with moderate renal failure (creatinine clearance 30-60 ml/min), the use of Rosucard® at a dose of 40 mg/day is contraindicated.

In patients with mild renal failure, no dose adjustment is required; The recommended initial dose of Rosucard® is 5 mg/day.

Use for liver dysfunction

Restrictions for liver dysfunction - With caution.

The drug is contraindicated in patients with active liver disease.

The drug should be prescribed with caution if there is a history of liver disease.

Use in elderly patients

Restrictions for elderly patients - Use with caution.

The drug should be prescribed with caution to patients over 65 years of age.

Use in children

Restrictions for children - Contraindicated.

The use of the drug is contraindicated in people under 18 years of age (efficacy and safety have not been established).

Terms of sale

The drug is available with a prescription.

Contacts for inquiries

SANOFI (Unknown)

Representative office of JSC "Sanofi-aventis group" (France) 125009 Moscow, st. Tverskaya, 22 Tel. Fax

Interaction

Transport protein inhibitors: rosuvastatin binds to some transport proteins, in particular OATP1B1 and BCRP. Concomitant use of drugs that are inhibitors of these transport proteins may be accompanied by an increase in the concentration of rosuvastatin in the blood plasma and an increased risk of developing myopathy (see table 3 and “Method of administration and dosage” and “Special instructions”).

Fusidic acid: There are no specific drug interaction studies between fusidic acid and rosuvastatin, but there have been isolated case reports of rhabdomyolysis.

Vitamin K antagonists: Initiating therapy or increasing the dose of Rosucard® in patients receiving concomitant vitamin K antagonists (eg warfarin) may lead to an increase in the INR.

Discontinuation or reduction of the dose of Rosucard® may lead to a decrease in the INR. In such cases, INR monitoring is recommended.

The simultaneous use of rosuvastatin and cyclosporine does not affect the plasma concentration of cyclosporine, however, the effect of rosuvastatin is enhanced (its elimination slows down, AUC increases by 7 times, Cmax increases by 11 times).

Erythromycin increases intestinal motility, which leads to a decrease in the effect of rosuvastatin (AUC decreases by 20% and Cmax by 30%).

In patients receiving vitamin K antagonists (eg warfarin), INR monitoring is recommended, since initiation of rosuvastatin therapy or increasing the dose of the drug may lead to an increase, and discontinuation of rosuvastatin or reducing its dose may lead to a decrease.

Gemfibrozil enhances the effect of rosuvastatin (increases Cmax and AUC by 2 times).

The simultaneous use of rosuvastatin and antacids containing aluminum and magnesium hydroxide leads to a decrease in the plasma concentration of rosuvastatin by approximately 50%. This effect is less pronounced if antacids are used 2 hours after taking rosuvastatin.

The simultaneous use of rosuvastatin and oral contraceptives increases the AUC of ethinyl estradiol and AUC of norgestrel by 26 and 34%, respectively, which should be taken into account when selecting the dose of oral contraceptives. There are no pharmacokinetic data on the simultaneous use of rosuvastatin and hormone replacement therapy; therefore, a similar effect cannot be excluded when using this combination.

The research results showed that rosuvastatin is neither an inhibitor nor an inducer of cytochrome P450 isoenzymes. Rosuvastatin is a non-core substrate for these isoenzymes. No clinically significant interactions were observed with drugs such as fluconazole, ketoconazole and itraconazole, which are metabolized by the cytochrome P450 system.

There is no clinically significant interaction between rosuvastatin and digoxin or fenofibrate.

Gemfibrozil, other fibrates and lipid-lowering doses of nicotinic acid (not <1 g/day) increased the risk of myopathy when used simultaneously with other HMG-CoA reductase inhibitors. Possibly due to the fact that they can cause myopathy when used as monotherapy.

Co-administration of rosuvastatin and ezetimibe did not result in changes in the AUC or Cmax of both drugs.

The use of HIV protease inhibitors with rosuvastatin can lead to a significant increase in the effect of rosuvastatin. A pharmacokinetic study of co-administration of 20 mg rosuvastatin and a combination of two HIV protease inhibitors (400 mg lopinavir/100 mg ritonavir) in healthy volunteers showed approximately 2- and 5-fold increases in AUC0-24 and Cmax, respectively. Therefore, co-administration of rosuvastatin with HIV protease inhibitors is not recommended in patients infected with HIV.

Rozucard®

Effect of the use of other drugs on rosuvastatin
Transport protein inhibitors:

rosuvastatin binds to some transport proteins, in particular OATP1B1 and BCRP. Concomitant use of drugs that are inhibitors of these transport proteins may be accompanied by an increase in the concentration of rosuvastatin in the blood plasma and an increased risk of developing myopathy (see Table 3 and sections “Dosage and Administration” and “Special Instructions”).

Cyclosporine:

with simultaneous use of rosuvastatin and cyclosporine, the AUC of rosuvastatin was on average 7 times higher than the value observed in healthy volunteers (see Table 3). Does not affect plasma concentrations of cyclosporine. Rosucard® is contraindicated in patients taking cyclosporine (see section "Contraindications").

Human immunodeficiency virus (HIV) protease inhibitors:

Although the exact mechanism of interaction is unknown, coadministration of HIV protease inhibitors may result in a significant increase in rosuvastatin exposure (see Table 3). A pharmacokinetic study of the simultaneous use of 20 mg rosuvastatin with a combination drug containing two HIV protease inhibitors (400 mg lopinavir/100 mg ritonavir) in healthy volunteers resulted in an approximately two-fold and five-fold increase in AUC(o_24) and Cmax of rosuvastatin, respectively. Therefore, simultaneous use of the drug Rosucard® and HIV protease inhibitors is not recommended (see sections “Method of administration and dosage”, “Special instructions”, table 3).

Gemfibrozil and other lipid-lowering drugs:

The combined use of rosuvastatin and gemfibrozil leads to a 2-fold increase in the Cmax and AUC of rosuvastatin (see section “Special Instructions”). Based on specific interaction data, a pharmacokinetically significant interaction with fenofibrate is not expected; a pharmacodynamic interaction is possible. Gemfibrozil, fenofibrate, other fibrates and lipid-lowering doses of nicotinic acid (more than 1 g per day) increased the risk of myopathy when used concomitantly with HMG-CoA reductase inhibitors, possibly due to the fact that they can cause myopathy when used in monotherapy (see . section "Special instructions"). When taking the drug simultaneously with gemfibrozil, fibrates, nicotinic acid in lipid-lowering doses, patients are recommended to take an initial dose of Rosucard® 5 mg; taking a dose of 40 mg is contraindicated when co-administered with fibrates (see sections “Contraindications”, “Dosage and Administration”, "Special instructions").

Fusidic acid:

There have been no specific drug interaction studies between fusidic acid and rosuvastatin, but isolated case reports of rhabdomyolysis have been noted.

Ezetimibe:

simultaneous use of Rosucard® at a dose of 10 mg and ezetimibe at a dose of 10 mg was accompanied by an increase in the AUC of rosuvastatin in patients with hypercholesterolemia (see Table 3). An increased risk of side effects due to the pharmacodynamic interaction between Rosucard® and ezetimibe cannot be excluded.

Antacids:

simultaneous use of rosuvastatin and antacid suspensions containing magnesium and aluminum hydroxide leads to a decrease in the plasma concentration of rosuvastatin by approximately 50%. This effect is less pronounced if antacids are used 2 hours after taking rosuvastatin. The clinical significance of this interaction has not been studied.

Erythromycin:

simultaneous use of rosuvastatin and erythromycin leads to a decrease in AUC of rosuvastatin by 20% and Cmax of rosuvastatin by 30%. This interaction may occur as a result of increased intestinal motility caused by erythromycin.

Isoenzymes of the cytochrome P450 system:

in vivo
and
in vitro
studies showed that rosuvastatin is neither an inhibitor nor an inducer of isoenzymes of the cytochrome P450 system. In addition, rosuvastatin is a weak substrate for these isoenzymes. Therefore, interaction of rosuvastatin with other drugs at the metabolic level involving isoenzymes of the cytochrome P450 system is not expected. There was no clinically significant interaction of rosuvastatin with fluconazole (an inhibitor of the CYP2C9 and CYP3A4 isoenzymes) and ketoconazole (an inhibitor of the CYP2A6 and CYP3A4 isoenzymes).

Interactions with drugs that require dose adjustment of rosuvastatin (see Table 3)

The dose of Rosucard® should be adjusted if it is necessary to use it together with drugs that increase the exposure of rosuvastatin. If an increase in exposure by 2 times or more is expected, the initial dose of Rosucard® should be 5 mg once daily. The maximum daily dose of Rosucard® should also be adjusted so that the expected exposure to rosuvastatin does not exceed that for a dose of 40 mg taken without the simultaneous administration of drugs that interact with rosuvastatin. For example, the maximum daily dose of Rosucard® when used simultaneously with gemfibrozil is 20 mg (increased exposure by 1.9 times), with ritonavir/atazanavir - 10 mg (increased exposure by 3.1 times).

Table 3. Effect of concomitant therapy on rosuvastatin exposure (AUC, data in descending order) - results from published clinical studies.

The effect of rosuvastatin on other drugs.

Vitamin K antagonists:

Initiating therapy or increasing the dose of Rosucard® in patients receiving concomitant vitamin K antagonists (for example, warfarin) may lead to an increase in the International Normalized Ratio (INR). Discontinuation or reduction of the dose of Rosucard® may lead to a decrease in the INR. In such cases, INR monitoring is recommended.

Oral contraceptives/hormone replacement therapy:

simultaneous use of rosuvastatin and oral contraceptives increases the AUC of ethinyl estradiol and AUC of norgestrel by 26% and 34%, respectively. This increase in plasma concentration should be taken into account when selecting the dose of oral contraceptives. There are no pharmacokinetic data on the simultaneous use of Rosucard® and hormone replacement therapy; therefore, a similar effect cannot be excluded when using this combination. However, this combination was widely used during clinical trials and was well tolerated by patients.

Other medicines:

No clinically significant interaction between rosuvastatin and digoxin is expected.

Directions for use and doses

Inside, without chewing or crushing, swallow whole with water, at any time of the day, regardless of meals.

Before starting therapy with Rosucard®, the patient should begin to follow a standard lipid-lowering diet and continue to follow it during treatment. The dose of the drug should be adjusted individually, depending on the indication and therapeutic response, taking into account current generally accepted recommendations for target lipid levels. If it is necessary to take the drug at a dose of 5 mg, the 10 mg tablet should be divided into 2 parts according to the risk.

The recommended starting dose of Rosucard® for patients starting to take the drug, or for patients transferred from taking other HMG-CoA reductase inhibitors, is 5 or 10 mg 1 time per day.

When choosing the initial dose, one should be guided by the patient’s cholesterol level and take into account the risk of developing cardiovascular complications, and it is also necessary to assess the potential risk of side effects. If necessary, after 4 weeks the dose of the drug can be increased.

Due to the potential for side effects when taking a dose of 40 mg compared to lower doses of the drug (see "Side Effects"), final titration to a maximum dose of 40 mg should only be done in patients with severe hypercholesterolemia and a high risk of cardiovascular complications (especially in patients with hereditary hypercholesterolemia) in whom the target cholesterol level was not achieved when taking a dose of 20 mg and who will be under medical supervision. Particularly careful monitoring of patients receiving the drug at a dose of 40 mg is recommended.

It is not recommended to prescribe a dose of 40 mg to patients who have not previously consulted a doctor. After 2–4 weeks of therapy and/or when the dose of Rosucard® is increased, it is necessary to monitor lipid metabolism parameters (if necessary, dose adjustment is required).

Patients with liver failure. In patients with liver failure with Child-Pugh scores below 7 points, no dose adjustment of Rosucard® is required. The drug Rosucard® is contraindicated in patients with liver disease in the active phase, a persistent increase in serum activity of liver transaminases (more than 3 times compared to ULN) of unknown origin and patients with liver failure (severity from 7 to 9 points on the Child-Pugh scale ) (see “Contraindications”).

Patients with renal failure. In patients with mild renal failure, no dose adjustment is required. The recommended initial dose of Rosucard® is 5 mg/day.

In patients with severe renal failure (creatinine clearance <30 ml/min), the use of Rosucard® is contraindicated.

In patients with moderate renal failure (creatinine clearance 30–60 ml/min), the use of Rosucard® at a dose of 40 mg/day is contraindicated (see “Contraindications”).

Elderly patients. In patients over 65 years of age, no dose adjustment is required.

Special populations

Patients with a predisposition to myopathy. The use of Rosucard® at a dose of 40 mg/day is contraindicated in patients with a predisposition to myopathy (see “Contraindications”). When prescribing doses of 10 and 20 mg/day, the recommended initial dose of Rosucard® for this group of patients is 5 mg/day.

Ethnic groups. When studying the pharmacokinetic parameters of rosuvastatin, an increase in the systemic concentration of the drug was noted in representatives of the Mongoloid race (see “Pharmacokinetics”).

This fact should be taken into account when prescribing Rosucard® to patients of the Mongoloid race. When prescribing doses of 10 and 20 mg, the recommended initial dose of Rosucard® for this group of patients is 5 mg/day. The use of the drug Rosucard® at a dose of 40 mg/day in representatives of the Mongoloid race is contraindicated (see “Contraindications”).

When prescribing Rosucard® with gemfibrozil, the dose should not exceed 10 mg/day.

Genetic polymorphism. Carriers of the SLCO1B1 (OATP1B1) c.521CC and ABCG2 (BCRP) c.421AA genotypes showed an increase in exposure (AUC) to rosuvastatin compared to carriers of the SLC01B1 c.521TT and ABCG2 c.421CC genotypes. For patients carrying genotypes c.521CC or c.421AA, the recommended maximum dose of Rosucard® is 20 mg/day (see “Pharmacokinetics”, “Special instructions” and “Interaction”).

Concomitant therapy. Rosucard® binds to various transport proteins (in particular, OATP1B1 and BCRP). When simultaneous use of the drug Rosucard® with drugs (such as cyclosporine, some HIV protease inhibitors, including a combination of ritonavir with atazanavir, lopinavir and/or tipranavir) that increase the concentration of rosuvastatin in the blood plasma due to interaction with transport proteins, the risk of developing myopathy may increase (including rhabdomyolysis) (see “Special Instructions” and “Interaction”). In such cases, the possibility of prescribing alternative therapy or temporarily stopping the use of Rosucard® should be assessed. If the use of the above drugs is necessary, you should read the instructions for use of the drugs before prescribing them simultaneously with the drug Rosucard®, assess the benefit-risk ratio of concomitant therapy and consider reducing the dose of the drug Rosucard® (see “Interaction”).

Instructions for use of ROSUCARD®

Renal dysfunction

Proteinuria, detected using a test strip and mainly tubular in origin, was observed in patients receiving rosuvastatin in higher doses, namely 40 mg. Proteinuria is not a precursor to the development of acute or progressive renal failure. The incidence of serious renal impairment observed in post-marketing studies was higher at the 40 mg dose. Renal function should be assessed during routine examination of patients receiving the drug at a dose of 40 mg.

Musculoskeletal disorders

Musculoskeletal side effects such as myalgia, myopathy and, rarely, rhabdomyolysis have been observed in patients receiving rosuvastatin at any dose, particularly at doses greater than 20 mg. Rare cases of rhabdomyolysis have been observed in patients receiving ezetimibe in combination with HMG-CoA reductase inhibitors. A pharmacodynamic interaction between these drugs cannot be ruled out and caution should be exercised when using them together. As with other HMG-CoA reductase inhibitors, post-marketing reports of rhabdomyolysis with rosuvastatin were primarily associated with rosuvastatin 40 mg.

Control of creatine phosphokinase (CPK)

CPK levels should not be measured after heavy physical activity or if there is another reason for the increase in CPK levels, because this may lead to incorrect results. If the initial CPK level is significantly elevated (5 times the ULN), a repeat test should be performed within 5-7 days. If a repeat analysis confirms that the CPK level exceeds 5 times the normal level, treatment cannot be started.

Before treatment

The administration of rosuvastatin, like other HMG-CoA reductase inhibitors, is indicated with caution in patients with predisposing factors to the development of myopathy/rhabdomyolysis. These factors are:

• renal failure;
• hypothyroidism;
• patient or family history of muscle disorders;
• Providing a toxic effect on the muscles earlier when taking another HMG-CoA reductase inhibitor or fibrate;
• alcohol addiction;
• age over 70 years;
• situations in which an increase in plasma concentrations is possible;
• combined use with fibrates.

In such patients, the risk of therapy must be weighed against the expected effect, and inpatient monitoring is recommended. If the initial CPK level exceeds 5 times the normal CPK level, treatment cannot be started.

During treatment

Patients are advised to immediately report unexplained muscle pain, lethargy, or weakness, especially if accompanied by malaise or fever. CPK levels should be measured in these patients. Treatment should be discontinued if CPK levels exceed 5 times the normal CPK level or if muscle side effects are significant and cause daily discomfort (even if CPK levels exceed 5 times the normal CPK level). If symptoms resolve and CPK levels return to normal, rosuvastatin therapy may be resumed or another HMG-CoA reductase inhibitor at the lowest dose may be prescribed with careful monitoring of the patient. Routine monitoring of CPK levels in patients without these symptoms is not necessary.

In clinical trials, there was no evidence of an increase in musculoskeletal side effects in a small group of patients receiving rosuvastatin in combination with other drugs. However, an increase in the incidence of myositis and myopathy has been observed in patients receiving other HMG-CoA reductase inhibitors with fibrates, including gemfibrozil, cyclosporine, niacin, azole antifungals, protease inhibitors and macrolides. The use of gemfibrozil in combination with HMG-CoA reductase inhibitors increases the risk of developing myopathy. Therefore, concomitant use of rosuvastatin with gemfibrozil is not recommended. When using rosuvastatin together with fibrates or niacin, there are possible risks of side effects that should be taken into account when prescribing such combinations. The use of rosuvastatin at a dose of 40 mg is contraindicated when used together with fibrates. Rosuvastatin should not be administered to patients with acute conditions predisposing to the development of myopathy or with a predisposition to the development of renal failure due to rhabdomyolysis (eg, sepsis, hypotension, surgery, trauma, metabolic, endocrine and electrolyte disorders; or uncontrolled seizures).

Side effects on the liver

Like other HMG-CoA reductase inhibitors, rosuvastatin should be used with caution in patients who consume excessive amounts of alcohol or have a history of liver disease. It is recommended to conduct a liver function test before starting treatment and during the first 3 months. In cases where the content of transaminases exceeds ULN by 3 times, treatment is canceled. The potential for liver effects (primarily increased transaminase levels) is greater at the 40 mg dose.

In patients with secondary hypercholesterolemia caused by hypothyroidism or nephrotic syndrome, treatment begins with compensation of the underlying disease (before starting rosuvastatin therapy).

Race

Pharmacokinetic studies have shown that the drug has a stronger effect on representatives of the Mongoloid race than on representatives of the Caucasian race.

Protease inhibitors

Concomitant use with protease inhibitors is not recommended.

Chronic lung diseases with connective tissue damage

Interstitial lung disease has been reported in exceptional cases with the use of some statins, especially during long-term treatment. Difficulty breathing, a dry cough, and general deterioration in health (fatigue, weight loss, and fever) may also occur. If interstitial lung disease is suspected, statin therapy should be discontinued.

Diabetes

Some evidence suggests that statins may increase blood glucose levels and, in patients predisposed to diabetes mellitus, may lead to a level of hyperglycemia at which diabetes treatment may be appropriate. However, the benefits of statin treatment outweigh this risk, and therefore discontinuation of statin therapy is not required. Patients at risk (fasting glucose level - 5.6-6.9 mmol/l, BMI>30 kg/m2, elevated triglyceride levels, hypertension) should be under careful clinical and biochemical supervision in accordance with national requirements. In a clinical study, the overall incidence of diabetes mellitus reports was 2.8% in the rosuvastatin group and 2.3% in the placebo group, mainly in patients with fasting glucose levels between 5.6 and 6.9 mmol/L.

Children

Assessment of linear growth (height), body weight, BMI (body mass index) and secondary characteristics of puberty using the Tanner scale in children aged 10 to 17 years taking rosuvastatin is limited to a period of 1 year. After 52 weeks of the study, there was no effect of rosuvastatin treatment on height, weight, BMI or puberty. Clinical experience with the drug in children and adolescents is limited, and the long-term effect of rosuvastatin (more than 1 year) on puberty is unknown.

In clinical trials in children and adolescents taking rosuvastatin for 52 weeks, CPK levels were elevated (>10 times ULN) and muscle symptoms were more common post-exercise or following increased physical activity compared with observations in clinical trials in adults.

The drug contains lactose monohydrate, therefore the use of rosuvastatin is contraindicated in patients with hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.

Impact on the ability to drive vehicles and operate machinery

Studies of the effect of rosuvastatin on the ability to drive a vehicle and control mechanical equipment have not been conducted. However, given the pharmacodynamic characteristics of the drug, caution should be exercised when driving vehicles or other mechanical vehicles (dizziness may occur during treatment with rosuvastatin).